NCCN Guideline Update in SCLC Adds Maintenance Lurbinectedin, Removes Chemotherapy-Free Interval

The National Comprehensive Cancer Care Network (NCCN) updated its small-cell lung cancer (SCLC) guidelines, incorporating 2 notable changes, among others: the addition of maintenance lurbinectedin (Zepzelca; Jazz Pharmaceuticals) in combination with atezolizumab (Tecentriq; Genentech) following first-line chemoimmunotherapy, and the removal of the chemotherapy-free interval (CTFI) from the subsequent-line systemic therapy algorithm.¹

Both updates have significant implications for pharmacists involved in treatment selection, patient counseling, and toxicity management.

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Addition of Lurbinectedin for First-Line Maintenance Therapy

For patients with extensive-stage SCLC (ES-SCLC), NCCN now recommends a new option: 4 cycles of induction carboplatin, etoposide, and atezolizumab, followed by maintenance with lurbinectedin (3.2 mg/m²) compared with its previous recommendation of atezolizumab alone in the maintenance setting.¹

Data from the IMforte trial supporting the use of lurbinectedin was presented at the American Society of Clinical Oncology 2025 meeting in Chicago. In the trial, 895 patients were screened for enrollment, and 660 (74%) were enrolled into the induction phase. Of those, 483 (73%) entered the maintenance phase and were randomly assigned to lurbinectedin plus atezolizumab (n = 242) or atezolizumab (n = 241).²

As of the data cutoff, progression-free survival (PFS) was longer in the combination therapy group than the atezolizumab group (stratified hazard ratio [HR] 0.54 [95% confidence interval 0.43-0.67]; P < .0001). Overall survival (OS) was also longer (stratified HR 0.73 [0.57-0.95]; P = 0.017).²

Pharmacists should note the elevated toxicity profile associated with the combination²:

• Grade 3 to 4 adverse events occurred in 38% of patients receiving the combination versus 22% with atezolizumab monotherapy
• Key toxicities included anemia (8%), neutropenia (7%), and thrombocytopenia (7%)
• Prophylactic use of granulocyte colony-stimulating factor (G-CSF) was mandated in the trial, highlighting the importance of supportive care planning

"One unique aspect of the IMForte trial is that patients also received growth factor support as primary prophylaxis, which is not something that is routinely recommended for patients receiving lurbinectedin in the relapsed/refractory setting," said Kevin Chen, PharmD, MS, BCOP, CPP, clinical pharmacist practitioner in thoracic oncology and sarcoma and assistant professor of clinical education at the University of North Carolina Medical Center in Chapel Hill. "This likely helped to reduce the myelosuppressive effects and it is therefore necessary to ensure patients receive this if they are receiving maintenance lurbinectedin."

Eligible patients include those with stable disease or better after induction, Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, and no history of brain metastases. Importantly, lurbinectedin cannot be reused in later lines of therapy if given as maintenance, reinforcing the need for pharmacists to anticipate sequencing implications.

Removal of the Chemotherapy-Free Interval

The updated guidelines eliminated the CTFI, historically used to distinguish platinum-sensitive versus platinum-resistant relapse and guide treatment selection. The qualifier and footnotes recommending platinum rechallenge for CTFI after more than 6 months were deleted.¹

This change reflects an evolving therapeutic landscape in which reliance on CTFI is less clinically meaningful. The recent DeLLphi-304 trial demonstrated that tarlatamab (Imdelltra; Amgen) significantly improved OS compared with chemotherapy (including lurbinectedin, topotecan, or amrubicin) in relapsed SCLC, with fewer grade 3 or higher adverse events (54% vs 80%).³ Such advances support a shift away from historical treatment algorithms toward evidence-based use of newer agents.

"In a way, the removal of CFTI from the guidelines makes it easier to remember what options are preferred for relapsed/refractory disease, with currently the category 1 preferred agent being tarlatamab," Chen said. "However, tarlatamab is not necessarily an easy medication for providers to administer or for patients to receive. Given its unique toxicity profile and necessity of close monitoring for [cytokine release syndrome/immune effector cell-associated neurotoxicity syndrome], there are still many institutions which do not have access to this medication."

Chen added that tarlatamab requires hospitalization and prolonged monitoring periods, a rigorous schedule, and robust caregiver support. Despite these challenges, however, he called tarlatamab a "very exciting new treatment" thanks to its meaningful central nervous system activity, possibility for durable disease control, and similar efficacy regardless of cytotoxic sensitivity.

"With all of these considerations, pharmacists can play a vital role in helping providers select which patient is the ideal candidate for which treatment, be it platinum retreatment, lurbinectedin, or tarlatamab," Chen said.

For pharmacists, this update underscores the need to reassess how subsequent-line therapies are selected and sequenced, stay current on emerging efficacy and toxicity data for novel agents, and counsel providers and patients on shifting expectations in relapsed/refractory SCLC.

What Do Pharmacists Need to Know?

These NCCN updates emphasize 2 pivotal shifts¹:

1. Earlier use of lurbinectedin in combination maintenance with atezolizumab, requiring vigilance around hematologic toxicities and supportive care.
2. Abandonment of the CTFI, signaling a more individualized approach to subsequent-line therapy selection, particularly in the context of novel options like tarlatamab.

"As we are using more novel therapies such as bispecific t-cell engagers routinely in the treatment of patients with SCLC, I think it's critical to develop a better understanding of acute toxicities such as CRS/ICANS as well as the chronic toxicities such as taste and appetite changes," Chen said. "It's important for pharmacists to understand the symptom onset and presentation so they are able to appropriately educate patients and family members on monitoring for these toxicities."

Pharmacists remain central to optimizing therapy, anticipating toxicities, and supporting evidence-based treatment decisions as the SCLC treatment paradigm continues to evolve.

REFERENCES

1. NCCN Clinical Practice Guidelines in Oncology: Small Cell Lung Cancer, Version 2.2026. National Comprehensive Cancer Network. Updated September 16, 2025. Accessed September 17, 2025. https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf

2. Paz-Ares L, Borghaei H, Liu SV, et al. Efficacy and safety of first-line maintenance therapy with lurbinectedin plus atezolizumab in extensive-stage small-cell lung cancer (IMforte): a randomized, multicentre, open-label, phase 3 trial. The Lancet. 2025;405(10495):2129-2143. doi:10.1016/S0140-6736(25)01011-6

3. Mountzios G, Sun L, Cho BC, et al. Tarlatamab in small-cell lung cancer after platinum-based chemotherapy. N Engl J Med. 2025;393:349-361. doi:10.1016/NEJMoa2502099